Certain disease states require treatment using one or more different medicaments. Some drug compounds need to be delivered in a specific relationship with each other in order to deliver the optimum therapeutic dose. The disclosed method and system is of particular benefit where combination therapy is desirable, but not possible in a single formulation for reasons such as, but not limited to, stability, compromised therapeutic performance and toxicology.
For example, in some cases it might be beneficial to treat a diabetic with a long acting insulin and with a glucagon-like peptide-1 (GLP-1), which is derived from the transcription product of the proglucagon gene. GLP-1 is found in the body and is secreted by the intestinal L cell as a gut hormone. GLP-1 possesses several physiological properties that make it (and its analogs) a subject of intensive investigation as a potential treatment of diabetes mellitus.
There are a number of potential problems when delivering two active medicaments or “agents” simultaneously. The two active agents may interact with each other during the long-term, shelf life storage of the formulation. Therefore, it is advantageous to store the active components separately and only combine them at the point of delivery, e.g. injection, needle-less injection, pumps, or inhalation. However, the process for combining the two agents needs to be simple and convenient for the user to perform reliably, repeatedly and safely.
A further problem is that the quantities and/or proportions of each active agent making up the combination therapy may need to be varied for each user or at different stages of their therapy. For example, one or more actives may require a titration period to gradually introduce a patient to a “maintenance” dose. A further example would be if one active requires a non-adjustable fixed dose while the other is varied in response to a patient's symptoms or physical condition. This problem means that pre-mixed formulations of multiple active agents may not be suitable as these pre-mixed formulations would have a fixed ratio of the active components, which could not be varied by the healthcare professional or user.
Additional problems arise where a multi-drug compound therapy is required, because many users cannot cope with having to use more than one drug delivery system or make the necessary accurate calculation of the required dose combination. This is especially true for users with dexterity or computational difficulties.
An additional issue that may arise is a potentially high dispense force required to inject a drug compound or two drug compounds. Dispense force is generally proportional to the amount of fluid being dispensed over a given time and the resistance (e.g., hydraulic resistance) through the device. A higher dose may therefore require a higher dispense force. Further, because a dual injection device injects two drug compounds rather than a single drug compound, the dispense force required by a dual injection device may be higher than a dispense force required by a typical single compound drug delivery device. For instance, dual injection devices may also have to overcome two sets of delivery mechanism frictions or two bungs moving in two cartridges.
Fully automatic devices may reduce or eliminate the force required to inject a drug compound or two drug compounds. However, fully automatic devices that have the capability to fully inject all drug compounds may experience ‘push-back’ from some users due to the lack of user control during dispensing. For example, certain users/patients express the desire or need to have at least a given level of control over the dispensing process (e.g., be required to use some manual input to dispense the drugs). Fully automatic devices have the further disadvantage of having to exert a high magnitude of force to account for the force variability and the requirement to ensure sufficient margin between the force delivered and the force required in all dose scenarios.
Accordingly, there exists a strong need to provide devices and methods for the delivery of two or more medicaments in a single injection or delivery step that is simple for the user to perform. Further, there exists a need to provide devices and methods that reduce the dispense force for delivery of two or more medicaments in a single injection or delivery step, while at the same time allowing the user a degree of control over the dispense.
The disclosed method and system overcomes the above-mentioned problems by providing separate storage containers for two or more active drug agents that are then only combined and/or delivered to the patient during a single delivery procedure. The disclosed method and system also provides a trigger, that is operably connected to a biasing member, such as a spring, that is configured to reduce the dispense force required by the device. Setting a dose of one medicament automatically fixes or determines the dose of the second medicament (i.e. non-user settable). The disclosed method and system also gives the opportunity for varying the quantity of one or both medicaments. For example, one fluid quantity can be varied by changing the properties of the injection device (e.g. dialing a user variable dose or changing the device's “fixed” dose). The second fluid quantity can be changed by manufacturing a variety of secondary drug containing packages with each variant containing a different volume and/or concentration of the second active agent. The user or healthcare professional would then select the most appropriate secondary package or series or combination of series of different packages for a particular treatment regime. Alternatively, the second fluid quantity can be changed by varying the properties of the fixed dose mechanism. The disclosed system and method may achieve a wide variety of target therapeutic profiles. For example, the disclosed system and method may achieve a therapeutic profile that delivers a fixed dose of a secondary medicament once a minimum setting threshold dose of a primary medicament has been set. The disclosed system and method also may add an element of auto-assistance that reduces the dispense force for the injection of two (or more) drug compounds while allowing the user a degree of control over the dispense process.
These and other advantages will become evident from the following more detailed description of the invention.